Pupillo is best known for his work as a horror film director in the 1960s and 1970s. His three most famous horror films were all made in 1965. He directed Terror-Creatures from the Grave (aka "Five Graves For A Medium") in 1965 which starred Barbara Steele. Pupillo also directed two other horror films that same year, Bloody Pit of Horror (starring Mickey Hargitay) and La vendetta di Lady Morgan.